Visfatin/PBEF/Nampt induces EMMPRIN and MMP-9 production in macrophages via the NAMPT-MAPK (p38, ERK1/2)-NF-κB signaling pathway

  • Authors:
    • Yuqi Fan
    • Shu Meng
    • Yue Wang
    • Jiatian Cao
    • Changqian Wang
  • View Affiliations

  • Published online on: February 15, 2011     https://doi.org/10.3892/ijmm.2011.621
  • Pages: 607-615
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The adipocytokine visfatin is closely associated with metabolic disorders. This study explored the effects of visfatin on macrophage-induced inflammation in atheroma. The ability of visfatin to enhance extracellular matrix metalloproteinase inducer (EMMPRIN) expression, matrix metalloproteinase-9 (MMP-9) production and enzymatic activity in THP-1 derived macrophages as well as the mechanisms involved were investigated. EMMPRIN and MMP-9 mRNA levels were investigated by RT-PCR. EMMPRIN and MMP-9 protein levels, nuclear factor (NF)-κB -p65 protein levels, peroxisome proliferator-activated receptor γ (PPARγ) protein levels, and mitogen-activated protein kinase (MAPK) phosphorylation were determined by Western blotting. MMP-9 enzymatic activity was assayed by gelatin zymography. Visfatin (50-400 ng/ml) induced EMMPRIN and MMP-9 depending on the dosage used. Visfatin elicited the activation of NF-κB and MAPK (p38, ERK1/2). Exogenous nicotinamide mononucleotide (NMN), the product of nicotinamide phosphoribosyltransferase (NAMPT) activity, mimicked the effects of visfatin on MAPK (p38, ERK1/2)-NF-κB activation and EMMPRIN/MMP-9 induction. Using the p38 inhibitor, SB203580, the ERK1/2 inhibitor PD98059, the NF-κB inhibitor, pyrrolidine dithiocarbamate and the NAMPT inhibitor FK866, we demonstrated that the visfatin pro-inflammatory action was through the NAMPT-MAPK (p38, ERK1/2)-NF-κB pathway. Furthermore, the visfatin pro-inflammatory action was not prevented by insulin receptor blockade or by a PPARγ agonist. Visfatin did not modulate PPARγ expression. Retinoid X receptor (RXR) agonist suppressed the effects of visfatin on EMMPRIN/MMP-9, NF-κB, but not on MAPK activation. In conclusion, we have demonstrated that visfatin enhances atheroma inflammation through the NAMPT-MAPK (p38, ERK1/2)-NF-κB-EMMPRIN/MMP-9 pathway, a key feature of atherosclerotic diseases linked to metabolic disorders.

Related Articles

Journal Cover

April 2011
Volume 27 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Fan Y, Meng S, Wang Y, Cao J and Wang C: Visfatin/PBEF/Nampt induces EMMPRIN and MMP-9 production in macrophages via the NAMPT-MAPK (p38, ERK1/2)-NF-κB signaling pathway. Int J Mol Med 27: 607-615, 2011.
APA
Fan, Y., Meng, S., Wang, Y., Cao, J., & Wang, C. (2011). Visfatin/PBEF/Nampt induces EMMPRIN and MMP-9 production in macrophages via the NAMPT-MAPK (p38, ERK1/2)-NF-κB signaling pathway. International Journal of Molecular Medicine, 27, 607-615. https://doi.org/10.3892/ijmm.2011.621
MLA
Fan, Y., Meng, S., Wang, Y., Cao, J., Wang, C."Visfatin/PBEF/Nampt induces EMMPRIN and MMP-9 production in macrophages via the NAMPT-MAPK (p38, ERK1/2)-NF-κB signaling pathway". International Journal of Molecular Medicine 27.4 (2011): 607-615.
Chicago
Fan, Y., Meng, S., Wang, Y., Cao, J., Wang, C."Visfatin/PBEF/Nampt induces EMMPRIN and MMP-9 production in macrophages via the NAMPT-MAPK (p38, ERK1/2)-NF-κB signaling pathway". International Journal of Molecular Medicine 27, no. 4 (2011): 607-615. https://doi.org/10.3892/ijmm.2011.621